![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Research Papers
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Abstract
Naturally occurring deletions that remove sequences located approximately 60 kb upstream of the human adult beta-globin gene result in the failure to transcriptionally activate the cis-linked globin genes in erythroid cells. In addition, transfection, transgenic, and somatic cell hybrid studies have revealed that sequences within this region are essential for the developmentally regulated high-level expression of cis-linked globin genes. This regulatory region located at the 5' end of the beta-globin locus has been termed the locus activation region (LAR). Using somatic cell hybrids, we have studied the chromatin structure and timing of DNA replication of the normal human beta-globin locus and a locus containing a de novo 25-kb deletion that removes elements of the LAR. As a result of this deletion, the entire beta-globin locus and sequences approximately 100 kb 5' and 3' of the adult beta-globin gene are DNase I-resistant and do not form characteristic distant hypersensitive sites. These sequences also replicate late in S phase in an erythroid cell background. In contrast, the sequences of the normal locus are DNase I sensitive and early replicating. These results suggest that the LAR is required for both the erythroid-specific chromatin structure and timing of DNA replication over a large physical distance.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. B. Palmer, P. Majumder, M. R. Green, P. A. Wade, and J. M. Boss A 3' Enhancer Controls Snail Expression in Melanoma Cells Cancer Res., July 1, 2007; 67(13): 6113 - 6120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Bender, R. Byron, T. Ragoczy, A. Telling, M. Bulger, and M. Groudine Flanking HS-62.5 and 3' HS1, and regions upstream of the LCR, are not required for beta-globin transcription Blood, August 15, 2006; 108(4): 1395 - 1401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhao, W. Zhou, G. Rank, R. Sutton, X. Wang, H. Cumming, L. Cerruti, J. M. Cunningham, and S. M. Jane Repression of human {gamma}-globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter Blood, March 1, 2006; 107(5): 2138 - 2145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Mahajan, G. J. Narlikar, G. Boyapaty, R. E. Kingston, and S. M. Weissman Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the {beta}-globin locus control region PNAS, October 18, 2005; 102(42): 15012 - 15017. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Diaz-Perez, Y. Ouyang, V. Perez, R. Cisneros, M. Regelson, and Y. Marahrens The Element(s) at the Nontranscribed Xist Locus of the Active X Chromosome Controls Chromosomal Replication Timing in the Mouse Genetics, October 1, 2005; 171(2): 663 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-Q. Feng, R. Warin, T. Li, E. Olivier, A. Besse, A. Lobell, H. Fu, C. M. Lin, M. I. Aladjem, and E. E. Bouhassira The Human {beta}-Globin Locus Control Region Can Silence as Well as Activate Gene Expression Mol. Cell. Biol., May 15, 2005; 25(10): 3864 - 3874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Stavropoulos, R. K. Rowntree, and J. T. Lee Identification of Developmentally Specific Enhancers for Tsix in the Regulation of X Chromosome Inactivation Mol. Cell. Biol., April 1, 2005; 25(7): 2757 - 2769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bottardi, V. Bourgoin, N. Pierre-Charles, and E. Milot Onset and inheritance of abnormal epigenetic regulation in hematopoietic cells Hum. Mol. Genet., February 15, 2005; 14(4): 493 - 502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Hiratani, A. Leskovar, and D. M. Gilbert Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores PNAS, November 30, 2004; 101(48): 16861 - 16866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Xiang, X. Ye, H. Han, M. Stafford, S. George, and Q. Li Juxtaposition of the HPFH2 Enhancer Is Not Sufficient To Reactivate the g-Globin Gene in Adult Erythropoiesis in bYAC Transgenic Mice. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 1215 - 1215. [Abstract]
|
|
|
|
 |
|
 W. Zhou, Q. Zhao, R. Sutton, H. Cumming, X. Wang, L. Cerruti, M. Hall, R. Wu, J. M. Cunningham, and S. M. Jane The Role of p22 NF-E4 in Human Globin Gene Switching J. Biol. Chem., June 18, 2004; 279(25): 26227 - 26232. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Patrinos, M. de Krom, E. de Boer, A. Langeveld, A.M. A. Imam, J. Strouboulis, W. de Laat, and F. G. Grosveld Multiple interactions between regulatory regions are required to stabilize an active chromatin hub Genes & Dev., June 15, 2004; 18(12): 1495 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Saha, Y. Shan, L. D. Mesner, and J. L. Hamlin The promoter of the Chinese hamster ovary dihydrofolate reductase gene regulates the activity of the local origin and helps define its boundaries Genes & Dev., February 15, 2004; 18(4): 397 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Cairns, E. Moroni, E. Levantini, A. Giorgetti, F. G. Klinger, S. Ronzoni, L. Tatangelo, C. Tiveron, M. De Felici, S. Dolci, et al. Kit regulatory elements required for expression in developing hematopoietic and germ cell lineages Blood, December 1, 2003; 102(12): 3954 - 3962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bulger, D. Schubeler, M. A. Bender, J. Hamilton, C. M. Farrell, R. C. Hardison, and M. Groudine A Complex Chromatin Landscape Revealed by Patterns of Nuclease Sensitivity and Histone Modification within the Mouse {beta}-Globin Locus Mol. Cell. Biol., August 1, 2003; 23(15): 5234 - 5244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. L. Kang, C. Mione Kiefer, and T. P. Yang Role of the Promoter in Maintaining Transcriptionally Active Chromatin Structure and DNA Methylation Patterns In Vivo Mol. Cell. Biol., June 15, 2003; 23(12): 4150 - 4161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-N. Prioleau, M.-C. Gendron, and O. Hyrien Replication of the Chicken {beta}-Globin Locus: Early-Firing Origins at the 5' HS4 Insulator and the {rho}- and {beta}A-Globin Genes Show Opposite Epigenetic Modifications Mol. Cell. Biol., May 15, 2003; 23(10): 3536 - 3549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Gribnau, K. Hochedlinger, K. Hata, E. Li, and R. Jaenisch Asynchronous replication timing of imprinted loci is independent of DNA methylation, but consistent with differential subnuclear localization Genes & Dev., March 15, 2003; 17(6): 759 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Onishi and R. Kiyama Interaction of NF-E2 in the Human beta -Globin Locus Control Region before Chromatin Remodeling J. Biol. Chem., February 28, 2003; 278(10): 8163 - 8171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Li, K. R. Peterson, X. Fang, and G. Stamatoyannopoulos Locus control regions Blood, October 16, 2002; 100(9): 3077 - 3086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Harju, K. J. McQueen, and K. R. Peterson Chromatin Structure and Control of {beta}-Like Globin Gene Switching Experimental Biology and Medicine, October 1, 2002; 227(9): 683 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Li, M. Zhang, H. Han, A. Rohde, and G. Stamatoyannopoulos Evidence that DNase I hypersensitive site 5 of the human {beta}-globin locus control region functions as a chromosomal insulator in transgenic mice Nucleic Acids Res., June 1, 2002; 30(11): 2484 - 2491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Navas, Q. Li, K. R. Peterson, R. A. Swank, A. Rohde, J. Roy, and G. Stamatoyannopoulos Activation of the {beta}-like globin genes in transgenic mice is dependent on the presence of the {beta}-locus control region Hum. Mol. Genet., April 15, 2002; 11(8): 893 - 903. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Aladjem, L. W. Rodewald, C. M. Lin, S. Bowman, D. M. Cimbora, L. L. Brody, E. M. Epner, M. Groudine, and G. M. Wahl Replication Initiation Patterns in the {beta}-Globin Loci of Totipotent and Differentiated Murine Cells: Evidence for Multiple Initiation Regions Mol. Cell. Biol., January 15, 2002; 22(2): 442 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Lorincz, D. Schubeler, and M. Groudine Methylation-Mediated Proviral Silencing Is Associated with MeCP2 Recruitment and Localized Histone H3 Deacetylation Mol. Cell. Biol., December 1, 2001; 21(23): 7913 - 7922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Sargent and J. A. Lloyd The Human gamma -Globin TATA and CACCC Elements Have Key, Distinct Roles in Suppressing beta -Globin Gene Expression in Embryonic/Fetal Development J. Biol. Chem., November 2, 2001; 276(45): 41817 - 41824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Plant, S. J. E. Routledge, and N. J. Proudfoot Intergenic Transcription in the Human {beta}-Globin Gene Cluster Mol. Cell. Biol., October 1, 2001; 21(19): 6507 - 6514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Bender, J. N. Roach, J. Halow, J. Close, R. Alami, E. E. Bouhassira, M. Groudine, and S. N. Fiering Targeted deletion of 5'HS1 and 5'HS4 of the {beta}-globin locus control region reveals additive activity of the DNaseI hypersensitive sites Blood, October 1, 2001; 98(7): 2022 - 2027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sawado, K. Igarashi, and M. Groudine Activation of beta -major globin gene transcription is associated with recruitment of NF-E2 to the beta -globin LCR and gene promoter PNAS, August 17, 2001; (2001) 181344198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Y. Gui and A. Dean Acetylation of a Specific Promoter Nucleosome Accompanies Activation of the {varepsilon}-Globin Gene by {beta}-Globin Locus Control Region HS2 Mol. Cell. Biol., February 15, 2001; 21(4): 1155 - 1163. [Abstract] [Full Text]
|
|
|
|
|
|
C. M. Farrell, A. Grinberg, S. P. Huang, D. Chen, J. G. Pichel, H. Westphal, and G. Felsenfeld A large upstream region is not necessary for gene expression or hypersensitive site formation at the mouse beta -globin locus PNAS, December 19, 2000; 97(26): 14554 - 14559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schübeler, M. C. Lorincz, D. M. Cimbora, A. Telling, Y.-Q. Feng, E. E. Bouhassira, and M. Groudine Genomic Targeting of Methylated DNA: Influence of Methylation on Transcription, Replication, Chromatin Structure, and Histone Acetylation Mol. Cell. Biol., December 15, 2000; 20(24): 9103 - 9112. [Abstract] [Full Text]
|
|
|
|
|
|
A. Heydemann, S. Warming, C. Clendenin, K. Sigrist, J. P. Hjorth, and M. C. Simon A minimal c-fes cassette directs myeloid-specific expression in transgenic mice Blood, November 1, 2000; 96(9): 3040 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhou, D. R. Clouston, X. Wang, L. Cerruti, J. M. Cunningham, and S. M. Jane Induction of Human Fetal Globin Gene Expression by a Novel Erythroid Factor, NF-E4 Mol. Cell. Biol., October 15, 2000; 20(20): 7662 - 7672. [Abstract] [Full Text]
|
|
|
|
|
|
D. M. Cimbora, D. Schübeler, A. Reik, J. Hamilton, C. Francastel, E. M. Epner, and M. Groudine Long-Distance Control of Origin Choice and Replication Timing in the Human beta -Globin Locus Are Independent of the Locus Control Region Mol. Cell. Biol., August 1, 2000; 20(15): 5581 - 5591. [Abstract] [Full Text]
|
|
|
|
|
|
V. M. Barbour, C. Tufarelli, J. A. Sharpe, Z. E. Smith, H. Ayyub, C. A. Heinlein, J. Sloane-Stanley, K. Indrak, W. G. Wood, and D. R. Higgs alpha -Thalassemia resulting from a negative chromosomal position effect Blood, August 1, 2000; 96(3): 800 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Forsberg, K. M. Downs, and E. H. Bresnick Direct interaction of NF-E2 with hypersensitive site 2 of the beta -globin locus control region in living cells Blood, July 1, 2000; 96(1): 334 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schübeler, C. Francastel, D. M. Cimbora, A. Reik, D. I.K. Martin, and M. Groudine Nuclear localization and histone acetylation: a pathway for chromatin opening and transcriptional activation of the human beta -globin locus Genes & Dev., April 15, 2000; 14(8): 940 - 950. [Abstract] [Full Text]
|
|
|
|
|
|
R. Bauchwitz and F. Costantini Developmentally distinct effects on human {varepsilon}-, {gamma}- and {delta}-globin levels caused by the absence or altered position of the human {beta}-globin gene in YAC transgenic mice Hum. Mol. Genet., March 1, 2000; 9(4): 561 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zappone, R Galli, R Catena, N Meani, S De Biasi, E Mattei, C Tiveron, A. Vescovi, R Lovell-Badge, S Ottolenghi, et al. Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells Development, January 6, 2000; 127(11): 2367 - 2382. [Abstract] [PDF]
|
|
|
|
|
|
W. Y. Chen and T. M. Townes Molecular mechanism for silencing virally transduced genes involves histone deacetylation and chromatin condensation PNAS, January 4, 2000; 97(1): 377 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. McDowell and A. Dean Structural and Functional Cross-Talk between a Distant Enhancer and the varepsilon -Globin Gene Promoter Shows Interdependence of the Two Elements in Chromatin Mol. Cell. Biol., November 1, 1999; 19(11): 7600 - 7609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Lee, M. R. Murphy, J.-S. Lee, and J. H. Chung Targeting a SWI/SNF-related chromatin remodeling complex to the beta -globin promoter in erythroid cells PNAS, October 26, 1999; 96(22): 12311 - 12315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Lee, C.-H. Lee, and J. H. Chung The beta -globin promoter is important for recruitment of erythroid Kruppel-like factor to the locus control region in erythroid cells PNAS, August 31, 1999; 96(18): 10051 - 10055. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Q. Feng, R. Alami, and E. E. Bouhassira Enhancer-Dependent Transcriptional Oscillations in Mouse Erythroleukemia Cells Mol. Cell. Biol., July 1, 1999; 19(7): 4907 - 4917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tumbar, G. Sudlow, and A. S. Belmont Large-Scale Chromatin Unfolding and Remodeling Induced by VP16 Acidic Activation Domain J. Cell Biol., June 28, 1999; 145(7): 1341 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bulger, J. H. von Doorninck, N. Saitoh, A. Telling, C. Farrell, M. A. Bender, G. Felsenfeld, R. Axel, and M. Groudine Conservation of sequence and structure flanking the mouse and human beta -globin loci: The beta -globin genes are embedded within an array of odorant receptor genes PNAS, April 27, 1999; 96(9): 5129 - 5134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Sargent, C. C. DuBois, A. M. Buller, and J. A. Lloyd The Roles of 5'-HS2, 5'-HS3, and the gamma -Globin TATA, CACCC, and Stage Selector Elements in Suppression of beta -Globin Expression in Early Development J. Biol. Chem., April 16, 1999; 274(16): 11229 - 11236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Bungert, K. Tanimoto, S. Patel, Q. Liu, M. Fear, and J. D. Engel Hypersensitive Site 2 Specifies a Unique Function within the Human beta -Globin Locus Control Region To Stimulate Globin Gene Transcription Mol. Cell. Biol., April 1, 1999; 19(4): 3062 - 3072. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Ortiz, D. Cado, and A. Winoto A New Element within the T-Cell Receptor alpha Locus Required for Tissue-Specific Locus Control Region Activity Mol. Cell. Biol., March 1, 1999; 19(3): 1901 - 1909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Saleque, M. Singh, and B. K. Birshtein Ig Heavy Chain Expression and Class Switching In Vitro from an Allele Lacking the 3' Enhancers DNase I-Hypersensitive hs3A and hs1,2 J. Immunol., March 1, 1999; 162(5): 2791 - 2803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sabbattini, A. Georgiou, C. Sinclair, and N. Dillon Analysis of Mice with Single and Multiple Copies of Transgenes Reveals a Novel Arrangement for the lambda 5-VpreB1 Locus Control Region Mol. Cell. Biol., January 1, 1999; 19(1): 671 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.A. Bender, A. Reik, J. Close, A. Telling, E. Epner, S. Fiering, R. Hardison, and M. Groudine Description and Targeted Deletion of 5' Hypersensitive Site 5 and 6 of the Mouse beta -Globin Locus Control Region Blood, December 1, 1998; 92(11): 4394 - 4403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Chattopadhyay, C. E. Whitehurst, and J. Chen A Nuclear Matrix Attachment Region Upstream of the T Cell Receptor beta Gene Enhancer Binds Cux/CDP and SATB1 and Modulates Enhancer-dependent Reporter Gene Expression but Not Endogenous Gene Expression J. Biol. Chem., November 6, 1998; 273(45): 29838 - 29846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Manis, N. van der Stoep, M. Tian, R. Ferrini, L. Davidson, A. Bottaro, and F. W. Alt Class Switching in B Cells Lacking 3' Immunoglobulin Heavy Chain Enhancers J. Exp. Med., October 19, 1998; 188(8): 1421 - 1431. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Reik, A. Telling, G. Zitnik, D. Cimbora, E. Epner, and M. Groudine The Locus Control Region Is Necessary for Gene Expression in the Human beta -Globin Locus but Not the Maintenance of an Open Chromatin Structure in Erythroid Cells Mol. Cell. Biol., October 1, 1998; 18(10): 5992 - 6000. [Abstract] [Full Text]
|
|
|
|
|
|
J. Zucman-Rossi, P. Legoix, J.-M. Victor, B. Lopez, and G. Thomas Chromosome translocation based on illegitimate recombination in human tumors PNAS, September 29, 1998; 95(20): 11786 - 11791. [Abstract] |
